Literature DB >> 22884950

Synergism between clofarabine and decitabine through p53R2: a pharmacodynamic drug-drug interaction modeling.

Karen E Thudium1, Sampa Ghoshal, Gerald J Fetterly, Jason P Den Haese, Adam R Karpf, Meir Wetzler.   

Abstract

Clofarabine (CLO), a purine nucleoside analog with promising efficacy in acute myeloid leukemia (AML), inhibits the ribonucleotidereductase, p53R2. We have shown that p53R2 mRNA is up-regulated by decitabine (DEC), another drug with promising activity in AML. We developed a pharmacodynamic model to characterize the interaction between CLO and DEC on an AML cell line and down-regulated p53R2 protein to understand its role. These results confirm a role for p53R2 in both CLO and DEC mechanism of action, demonstrate synergism between these two drugs in this AML model and support the use of this combination in a future clinical trial.
Copyright © 2012 Elsevier Ltd. All rights reserved.

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Year:  2012        PMID： 22884950      PMCID： PMC3457067          DOI： 10.1016/j.leukres.2012.07.015

Source DB:  PubMed          Journal:  Leuk Res        ISSN： 0145-2126            Impact factor:   3.156


  15 in total

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  1 in total

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